Pain control mechanism could be exploited as a new drug target

Researchers in Japan have revealed a previously unknown mechanism for pain control involving a newly identified group of cells in the spinal cord, offering a potential target for enhancing the therapeutic effect of drugs for chronic pain.

Although neurons may be the most prominent cells of the central nervous system, an assortment of non-neuronal cells first discovered in the mid-19th century also play a wide variety of important roles.

Originally named after the Greek word “glue”, glial cells are now known much more than glue, and in fact, they are critical elements for regulating neuronal development and function in the central nervous system.

Among the different types of glial cells, astrocytes are the most abundant in the central nervous system, however, unlike neurons in different brain regions, researchers have yet to develop a detailed understanding of groups of astrocytes with different properties.

Now, researchers led by Makoto Tsuda, professor at Kyushu University Graduate School of Pharmaceutical Sciences, have discovered a unique population of spinal cord astrocytes with a role in producing pain hypersensitivity.

Found in the outer two layers of gray matter near the back of the spinal cord – a place referred to as the superficial lamina of the spinal dorsal horn – the astrocytes are in an area known to carry general sensory information such as stress, pain . , And heat from around the body to the brain.

Using mice, the researchers showed that stimulating noradrenergic (naergic) neurons – so called for their use of noradrenaline as a neurotransmitter – carry signals from the locus corulus (LC) into the brain until the spinal dorsal horn activates the astrocytes Results in pain hypersensitivity.

These observations overturned the prevailing view that declining LC-NAergic neurons suppress pain transmission in the spinal dorsal horn.

“The discovery of this new population of astrocytes reveals a new role of declining LC-NAergic neurons in facilitating spinal pain transmission,” explains Zuda.

Considering these findings, suppressing signaling of the astrocytes by noradrenaline may enhance the effect of drugs for chronic pain.

To initially test this, the researchers genetically engineered mice in which response of astrocytes to noradrenaline was selectively inhibited and gave them duloxetine, an analgesic drug thought to increase levels of noradrenaline in the spinal cord by preventing uptake by lowering LC-Nerg.

Indeed, the modified mice exhibited an enhanced easing of chronic pain by duloxetine, after supporting the researchers’ proposed role of the astrocytes.

“Although we still need more studies with different drugs, the astrocyte population is a very promising target for enhancing the therapeutic potential of drugs for chronic pain,” says Zuda.

Reference: Kohro Y, Matsuda T, Yoshihara K. et al. Spinal astrocytes in superficial laminae portal brainstem decline control of mechanosensory hypersensitivity. Nat Neurosci 2020; 23: 1376-1387. Doi: 10.1038 / s41593-020-00713-4

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